scholarly journals Does Prenatal Methamphetamine Exposure Induce Cross-sensitization to Cocaine and Morphine in Adult Male Rats?

2012 ◽  
Vol 113 (3) ◽  
pp. 189-205 ◽  
Author(s):  
Romana Šlamberová ◽  
A. Yamamotová ◽  
M. Pometlová ◽  
B. Schutová ◽  
L. Hrubá ◽  
...  
Keyword(s):  
Adult Male ◽  
Analgesic Effect ◽  
Drug Exposure ◽  
Prenatal Drug Exposure ◽  
Male Rats ◽  
Daily Injection ◽  
Challenge Dose ◽  
Drug Seeking ◽  
Seeking Behavior ◽  
Plantar Test

The aim of the present study was to examine the cross-sensitization induced by prenatal methamphetamine (MA) exposure to challenge dose of cocaine or morphine. Rat mothers received a daily injection of MA (5 mg/kg) or saline throughout the gestation period. Adult male offspring (prenatally MA- or saline-exposed) were divided to groups with challenge doses of saline (1 ml/kg), cocaine (5 mg/kg) or morphine (5 mg/kg). Behavior in unknown environment was examined in Laboras, nociception in Plantar test, and active drug-seeking behavior in conditioned place preference (CPP). Our data demonstrate that cocaine increased the exploratory activity in Laboras test in prenatally saline-exposed, but decreased it in prenatally MA-exposed rats. An analgesic effect of cocaine was demonstrated only by the tail withdrawal and it was independent of the prenatal drug exposure. CPP test showed that prenatal MA exposure induced rather tolerance than sensitization to cocaine. In contrast to cocaine effects, morphine decreased rearing activity in both, prenatally MA-exposed and saline-exposed rats, and locomotion only in prenatally MA-exposed rats in the Laboras. In the Plantar test, the results demonstrated that morphine had an analgesic effect in prenatally saline-exposed rats but this effect was suppressed in prenatally MA-exposed rats. In the CPP test morphine induced drug-seeking behavior, which however was not affected by prenatal drug exposure. Thus, our data demonstrate that there is a cross-effect between prenatal MA exposure and the challenge dose of other drug in adulthood, however drug-seeking behavior is not increased by prenatal MA exposure as we expected.

scholarly journals Effect of Amphetamine on Adult Male and Female Rats Prenatally Exposed to Methamphetamine

2014 ◽  
Vol 115 (1-2) ◽  
pp. 43-59 ◽  
Author(s):  
Romana Šlamberová ◽  
Eva Macúchová ◽  
Kateryna Nohejlová ◽  
Andrea Štofková ◽  
Jana Jurčovičová
Keyword(s):  
Spatial Memory ◽  
Adult Male ◽  
Drug Exposure ◽  
Prenatal Drug Exposure ◽  
Female Rats ◽  
Male Rats ◽  
Daily Injection ◽  
Drug Seeking ◽  
Male And Female ◽  
Male And Female Rats

The aim of the present study was to examine the cross-sensitization induced by prenatal methamphetamine (MA) exposure to adult amphetamine (AMP) treatment in male and female rats. Rat mothers received a daily injection of MA (5 mg/kg) or saline throughout the gestation period. Adult male and female offspring (prenatally MA- or saline-exposed) were administered with AMP (5 mg/kg) or saline (1 ml/kg) in adulthood. Behaviour in unknown environment was examined in open field test (Laboras), active drug-seeking behaviour in conditioned place preference test (CPP), spatial memory in the Morris water maze (MWM), and levels of corticosterone (CORT) were analyzed by enzyme immunoassay (EIA). Our data demonstrate that in Laboras test, AMP treatment in adulthood increased general locomotion (time and distance travelled) regardless of the prenatal exposure and sex, while AMP increased exploratory activity (rearing) only in prenatally MA-exposed animals. AMP induced sensitization only in male rats, but not in females when tested drug-seeking behaviour in the CPP test. In the spatial memory MWM test, AMP worsened the performance only in females, but not in males. On the other hand, males swam faster after chronic AMP treatment regardless of the prenatal drug exposure. EIA analysis of CORT levels demonstrated higher level in females in all measurement settings. In males, prenatal MA exposure and chronic adult AMP treatment decreased CORT levels. Thus, our data demonstrated that adult AMP treatment affects behaviour of adult rats, their spatial memory and stress response in sex-specific manner. The effect is also influenced by prenatal drug exposure.

scholarly journals Do Prenatally Methamphetamine-Exposed Adult Male Rats Display General Predisposition to Drug Abuse in the Conditioned Place Preference Test?

2012 ◽  
pp. S129-S138
Author(s):  
R. ŠLAMBEROVÁ ◽  
M. POMETLOVÁ ◽  
B. SCHUTOVÁ ◽  
L. HRUBÁ ◽  
E. MACÚCHOVÁ ◽  
...  
Keyword(s):  
Drug Abuse ◽  
Pregnant Women ◽  
Conditioned Place Preference ◽  
Adult Male ◽  
Place Preference ◽  
Male Rats ◽  
Self Administration ◽  
Adult Rats ◽  
Drug Seeking ◽  
Seeking Behavior

Drug abuse of pregnant women is a growing problem. The effect of prenatal drug exposure may have devastating effect on development of the offsprings that may be long-term or even permanent. One of the most common drug abused by pregnant women is methamphetamine (MA), which is also the most frequently abused illicit drug in the Czech Republic. Our previous studies demonstrated that prenatal MA exposure alters behavior, cognition, pain and seizures in adult rats in sex-specific manner. Our most recent studies demonstrate that prenatal MA exposure makes adult rats more sensitive to acute injection of the same or related drugs than their controls. The aim of the present study was to examine the effect of prenatal MA exposure on drug-seeking behavior of adult male rats tested in the Conditioned place preference (CPP). Adult male rats were divided to: prenatally MA-exposed (5 mg/kg daily for the entire prenatal period), prenatally saline-exposed (1 ml/kg of physiological saline) and controls (without maternal injections). The following drugs were used in the CPP test in adulthood: MA (5 mg/kg), amphetamine (5 mg/kg), cocaine (5 and 10 mg/kg), morphine (5 mg/kg), MDMA (5 mg/kg) and THC (2 mg/kg). Our data demonstrated that prenatally MA-exposed rats displayed higher amphetamine-seeking behavior than both controls. MA as well as morphine induced drug-seeking behavior of adult male rats, however this effect did not differ based on the prenatal MA exposure. In contrast, prenatal MA exposure induced rather tolerance to cocaine than sensitization after the conditioning in the CPP. MDMA and THC did not induce significant effects. Even though the present data did not fully confirmed our hypotheses, future studies are planned to test the drug-seeking behavior also in self-administration test.

Does prenatal methamphetamine exposure affect the drug-seeking behavior of adult male rats?

2011 ◽  
Vol 224 (1) ◽  
pp. 80-86 ◽  
Author(s):  
Romana Šlamberová ◽  
Barbora Schutová ◽  
Lenka Hrubá ◽  
Marie Pometlová
Keyword(s):  
Adult Male ◽  
Male Rats ◽  
Drug Seeking ◽  
Seeking Behavior

scholarly journals Gender Differences in the Effect of Prenatal Methamphetamine Exposure and Challenge Dose of Other Drugs on Behavior of Adult Rats

2013 ◽  
pp. S99-S108 ◽  
Author(s):  
R. ŠLAMBEROVÁ ◽  
E. MACÚCHOVÁ ◽  
K. NOHEJLOVÁ-DEYKUN ◽  
B. SCHUTOVÁ ◽  
L. HRUBÁ ◽  
...  
Keyword(s):  
Estrous Cycle ◽  
Adult Male ◽  
Gonadal Hormones ◽  
Female Rats ◽  
Male Rats ◽  
Prenatally Exposed ◽  
Challenge Dose ◽  
Adult Rats ◽  
Male And Female ◽  
Male And Female Rats

The aim of the present study was to compare the response to acute application of several drugs in adult male and female rats prenatally exposed to methamphetamine (MA). Spontaneous locomotor activity and exploratory behavior of adult male and female rats prenatally exposed to MA (5 mg/kg) or saline were tested in a Laboras apparatus (Metris B.V., Netherlands) for 1 h. Challenge dose of the examined drug [amphetamine – 5 mg/kg; cocaine – 5mg/kg; MDMA (3,4-methylenedioxymethamphetamine) – 5 mg/kg; morphine – 5 mg/kg; THC (delta9-tetrahydrocannabinol) – 2 mg/kg] or saline was injected prior to testing. Our data demonstrate that prenatal MA exposure did not affect behavior in male rats with cocaine or morphine treatment, but increased locomotion and exploration in females. Application of amphetamine and MDMA in adulthood increased activity in both sexes, while cocaine and THC only in female rats. Morphine, on the other hand, decreased the activity in the Laboras test in both sexes. As far as sex and estrous cycle is concerned, the present study shows that males were generally less active than females and also females in proestrus-estrus phase of the estrous cycle were more active than females in diestrus. In conclusion, the present study shows that the prenatal MA exposure does not induce general sensitization but affects the sensitivity to drugs dependently to mechanism of drug action and with respect to gonadal hormones.

scholarly journals Does Prenatal Methamphetamine Exposure Induce Sensitization to Drugs in Adulthood?

2017 ◽  
pp. S457-S467 ◽  
Author(s):  
E. MACÚCHOVÁ ◽  
R. ŠLAMBEROVÁ
Keyword(s):  
Infant Development ◽  
Drug Exposure ◽  
Behavioral Sensitization ◽  
Drug Effects ◽  
Mechanisms Of Action ◽  
Prenatal Drug Exposure ◽  
Self Administration ◽  
Psychomotor Activity ◽  
Seeking Behavior ◽  
Reward Pathways

Behavioral sensitization is defined as augmented psychomotor activity, which can be observed after drug re-administration following withdrawal of repeated drug exposure. It has been shown that abuse of one drug can lead to increased sensitivity to certain other drugs. This effect of developed general drug sensitivity is called cross-sensitization and has been reported between drugs with similar as well as different mechanisms of action. There is growing evidence that exposure to drugs in utero not only causes birth defects and delays in infant development, but also impairs the neural reward pathways, in the brains of developing offspring, in such a way that it can increase the tendency for drug addiction later in life. This review summarizes the results of preclinical studies that focused on testing behavioral cross-sensitization, after prenatal methamphetamine exposure, to drugs administered in adulthood, with both similar and different mechanisms of action. Traditionally, behavioral sensitization has been examined using the Open field or the Laboras Test to record locomotor activity, and the Conditioned Place Preference and Self-administration test to examine drug-seeking behavior. However, it seems that prenatal drug exposure can sensitize animals not only to the locomotor-stimulating and conditioning effects of drugs, but may also be responsible for modified responses to various drug effects.

scholarly journals Inhibition of a cortico-thalamic circuit attenuates cue-induced reinstatement of drug-seeking behavior in “relapse prone” male rats

2020 ◽  
Author(s):  
Brittany N. Kuhn ◽  
Paolo Campus ◽  
Marin S. Klumpner ◽  
Stephen E. Chang ◽  
Amanda G. Iglesias ◽  
...  
Keyword(s):  
Individual Differences ◽  
Male Rats ◽  
Incentive Salience ◽  
Top Down ◽  
Drug Induced ◽  
Drug Seeking ◽  
Drug Cues ◽  
Cortical Input ◽  
Incentive Value ◽  
Seeking Behavior

AbstractRelapse often occurs when individuals are exposed to stimuli or cues previously associated with the drug-taking experience. The ability of drug cues to trigger relapse is believed to be a consequence of incentive salience attribution, a process by which the incentive value of reward is transferred to the reward-paired cue. Sign-tracker (ST) rats that attribute enhanced incentive value to reward cues are more prone to relapse compared to goal-tracker (GT) rats that primarily attribute predictive value to such cues. The neurobiological mechanisms underlying this individual variation in relapse propensity remains largely unexplored. The paraventricular nucleus of the thalamus (PVT) has been identified as a critical node in the regulation of cue-elicited behaviors in STs and GTs, including cue-induced reinstatement of drug-seeking behavior. Here we used a chemogenetic approach to assess whether “top-down” cortical input from the prelimbic cortex (PrL) to the PVT plays a role in mediating individual differences in relapse propensity. Chemogenetic inhibition of the PrL-PVT pathway selectively decreased cue-induced reinstatement of drug-seeking behavior in STs, without affecting behavior in GTs. In contrast, cocaine-primed drug-seeking behavior was not affected in either phenotype. Furthermore, when rats were characterized based on a different behavioral phenotype – locomotor response to novelty – inhibition of the PrL-PVT pathway had no effect on either cue- or drug-induced reinstatement. These results highlight an important role for the PrL-PVT pathway in vulnerability to relapse that is driven by individual differences in the propensity to attribute incentive salience to discrete reward cues.

scholarly journals Methamphetamine self-administration in a runway model of drug-seeking behavior in male rats

2018 ◽  
Vol 175 ◽  
pp. 27-32
Author(s):  
Mona Akhiary ◽  
Erin M. Purvis ◽  
Adam K. Klein ◽  
Aaron Ettenberg
Keyword(s):  
Male Rats ◽  
Self Administration ◽  
Drug Seeking ◽  
Seeking Behavior

scholarly journals Correction to: Inhibition of a cortico-thalamic circuit attenuates cue-induced reinstatement of drug-seeking behavior in “relapse prone” male rats

2021 ◽  
Author(s):  
Brittany N. Kuhn ◽  
Paolo Campus ◽  
Marin S. Klumpner ◽  
Stephen E. Chang ◽  
Amanda G. Iglesias ◽  
...  
Keyword(s):  
Male Rats ◽  
Drug Seeking ◽  
Seeking Behavior

scholarly journals Perinatal Stress and Methamphetamine Exposure Decreases Anxiety-Like Behavior in Adult Male Rats

2021 ◽  
Vol 15 ◽  
Author(s):  
Anna Holubová-Kroupová ◽  
Romana Šlamberová
Keyword(s):  
Water Stress ◽  
Adult Male ◽  
Drug Exposure ◽  
Maternal Separation ◽  
Cold Water ◽  
Male Rats ◽  
Central Disk ◽  
Postnatal Stress ◽  
Disk Area

Methamphetamine (MA) is an illicit synthetic psychostimulant drug, and its abuse is growing worldwide. MA has been reported as the primary drug of choice, by drug-abusing women, during pregnancy. Since MA easily crosses the placental barrier, the fetus is exposed to MA in a similar fashion to the mother. This study aimed to evaluate the effect of long-term perinatal stressors and drug exposure on anxiety-like behavior in adult male rats using the open field test (OF) and elevated plus maze (EPM). Dams were divided into three groups according to drug treatment during pregnancy: controls (C), saline—SA [subcutaneous (s.c.), 1 ml/kg], and MA (s.c., 5 mg/kg). Litters were divided into four groups according to postnatal stressors: non-stressed controls (N), maternal separation (S), maternal cold water stress (W), and maternal separation plus maternal cold water stress (SW). Forty-five minutes before testing (in both OF and EPM), one-half of adult male rats received an (s.c.) injection of MA and the other half received an SA injection. Prenatal MA/stress exposure did not affect anxiety-like behavior in adult male rats in both tests. In the OF, an acute MA dose in adulthood increased the time spent in the central disk area, decreased time spent in the corners, and decreased time spent immobile and grooming. Also, postnatal stress increased time spent in the central disk area, decreased time spent in corners, and increased mobility compared to controls. All groups of rats exposed to postnatal stressors spent significantly less time in the closed arms of the EPM compared to controls. Overall, our results indicate that early postnatal stress and a single acute MA administration in adulthood decreases the parameters of anxiety-like behavior in adult male rats regardless of prenatal MA exposure. Moreover, postnatal stress via maternal separation impacts the effect of acute MA administration in adulthood. Long-term postnatal stress may thus result in improved adaptation to subsequent stressful experiences later in life.

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